Estimates and Higher-Order Spectral Shift Measures in Several Variables

In recent years, higher-order trace formulas of operator functions have attracted considerable attention to a large part of the perturbation theory community. In this direction, we prove estimates for traces of higher-order derivatives of multivariable operator functions with associated scalar functions arising from multivariable analytic function space and, as a consequence, derive higher-order spectral shift measures for pairs of tuples of commuting contractions under Hilbert-Schmidt perturbations. These results substantially extend the main results of \cite{Sk15}, where the estimates were proved for traces of first and second-order derivatives of multivariable operator functions. In the context of the existence of higher-order spectral shift measures, our results extend the relative results of \cite{DySk09, PoSkSu14} from a single-variable to a multivariable setting under Hilbert-Schmidt perturbations. Our results rely crucially on heavy uses of explicit expressions of higher-order derivatives of operator functions and estimates of the divided deference of multivariable analytic functions, which are developed in this paper, along with the spectral theorem of tuples of commuting normal operators.Comment: 20 page

A clinical trial of treatment of uncomplicated typhoid fever: efficacy of ceftriaxone-azithromycin combination

Background: Typhoid fever is a systemic infection caused by Gram-negative bacterium Salmonella enterica serovar typhi (S. typhi). It is a major health problem in India. It carries significant morbidity and mortality. Antimicrobial therapy is critical for the management of typhoid fever. Emergence of multidrug-resistant (MDR) and nalidixic acid-resistant (NAR) strains of S. typhi has complicated therapy by limiting treatment options. Hence, this study was conducted to evaluate the efficacy and safety profile of ceftriaxone and azithromycin combination therapy in uncomplicated typhoid fever.Methods: Adults patients of blood culture proven uncomplicated typhoid fever admitted in the medicine ward of Teerthanker Mahaveer Medical College and Research Centre were treated with ceftriaxone intravenously (2 g daily for 14 days) and azithromycin orally (500 mg daily for 7 days). Patients were clinically and bacteriologically evaluated during the study period and follow-up.Results: 96% cure rate was observed. No relapse was recorded.Conclusion: Ceftriaxone-azithromycin combination may be considered as an empirical therapy for treatment of uncomplicated typhoid fever in view of the emergence of MDR and NAR strains of S. typhi

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Programmed Recognition between Complementary Dinucleolipids To Control the Self-Assembly of Lipidic Amphiphiles

This is the peer reviewed version of the following article: Morales‐Reina, S., Giri, C., Leclercq, M., Vela‐Gallego, S., de la Torre, I., Caston, J. R., ... & de la Escosura, A. (2020). Programmed Recognition between Complementary Dinucleolipids To Control the Self‐Assembly of Lipidic Amphiphiles. Chemistry–A European Journal, 26(5), 1082-1090, which has been published in final form at https://doi.org/10.1002/chem.201904217. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.One of the major goals in systems chemistry is to create molecular assemblies with emergent properties that are characteristic of life. An interesting approach toward this goal is based on merging different biological building blocks into synthetic systems with properties arising from the combination of their molecular components. The covalent linkage of nucleic acids (or their constituents: nucleotides, nucleosides and nucleobases) with lipids in the same hybrid molecule leads, for example, to the so-called nucleolipids. Herein, we describe nucleolipids with a very short sequence of two nucleobases per lipid, which, in combination with hydrophobic effects promoted by the lipophilic chain, allow control of the self-assembly of lipidic amphiphiles to be achieved. The present work describes a spectroscopic and microscopy study of the structural features and dynamic self-assembly of dinucleolipids that contain adenine or thymine moieties, either pure or in mixtures. This approach leads to different self-assembled nanostructures, which include spherical, rectangular and fibrillar assemblies, as a function of the sequence of nucleobases and chiral effects of the nucleolipids involved. We also show evidence that the resulting architectures can encapsulate hydrophobic molecules, revealing their potential as drug delivery vehicles or as compartments to host interesting chemistries in their interior.Research in Madrid received support from the Spanish Ministry of Economy and Competitivity (MINECO: CTQ‐2014‐53673‐P, CTQ‐2017‐89539‐P, and EUIN2017‐87022). This work was also supported in part by grants to JRC from MINECO (BFU2017‐88736‐R), and Comunidad Autónoma de Madrid (P2018/NMT‐4389). A.d.l.E. and M.S. thank the interdisciplinary framework provided by the European COST Action CM1304 (“Emergence and evolution of complex chemical systems”). A.d.l.E. and C.G. acknowledge the “Programme for Post‐Doctoral Talent Attraction to CEI UAM+CSIC—Intertalentum” (GA 713366). Research in Mons was supported by the Wallonia Region and the Fund for Scientific Research (FNRS, Belgium) under the grants MIS No. F.4532.16 (SHERPA) and EOS No. 30650939 (PRECISION). Confocal fluorescence microscopy was performed with the help of Sylvia Gutierrez Erlandsson, from the Advanced Light Microscopy Service of Centro Nacional de Biotecnologia (CNB). The professional editing service NB Revisions was used for technical preparation of the text prior to submission

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

An Improved Modulation Strategy for Fast Capacitor Voltage Balancing of Three-Level NPC Inverters

This paper presents an improved pulsewidth modulation strategy in conjunction with an optimal compensator for fast capacitor voltage balancing in three-level neutral-point-clamped (NPC) inverter. The voltage balancing compensator is designed in such a way that it produces optimal unbalance compensation coefficient according to the inherent limitations related to the variability range of modulating signals. It generates maximum compensating neutral current for the full modulation depth extending into overmodulation region and throughout the entire range of load power factor angles, and thus improves the unbalance compensation ability for all the operating conditions of the inverter. The optimal compensation offset signal corresponding to each operating point is determined from the boundary limit of the auxiliary modulating signals. Particle swarm optimization is applied for such purpose. The performance of the proposed optimal compensator for different combinations of modulation index and load power factors are evaluated through extensive simulation study using Matlab/Simulink and validated in experimentation using a threelevel NPC inverter prototype with induction motor load. Finally, the voltage balancing performances of the proposed compensator are compared with that available in literature to confirm the usefulness of the proposed concept

Mixed valence mono- and hetero-metallic grid catenanes

Here, we report on the multicomponent self-assembly and single crystal X-ray diffraction study of a series of three interlocked mixed valence mono- and hetero-metallic [2]-catenanes made of [2 2] metallo-grids. They show unique structural features and highlight the essential roles of both the Cu(II)/Cu(I) pair and of the conformationally adaptable organic ligands for achieving catenation of grids.peerReviewe

Self-assembly of a M4L6 complex with unexpected S4 symmetry

Using 1,4-diaminobenzene and 2-formylpyridine as simple building blocks results in a 1D ligand (rod, L2) to 2D (M4L4 grid, C1) to 3D (S4 symmetrical M4L6, C2) complexes upon sequential addition of Cu(I) and Fe(II) ions. The complex C2 can be seen as the smallest possible pseudo-tetrahedron with S4 symmetry.peerReviewe